D. A. Evans, F.

Michael General Reviews

An Introduction to Frontier Molecular Orbital Theory-1

Stereoelectronic Effects

Chem 531

Fleming, I. Frontier Orbitals and Organic Chemical Reactions Fukui, Acc. Chem. Res. 1971, 4, 57. Kirby, A. J. Stereoelectronic Effects.

Geometrical constraints placed upon ground and transition states by orbital overlap considerations.
Fukui Postulate for reactions: During the course of chemical reactions, the interaction of the highest filled (HOMO) and lowest unfilled (antibonding) molecular orbital (LUMO) in reacting species is very important to the stabilization of the transition structure.

Universal Effects Governing all Chemical Reactions

Steric Effects
Nonbonding interactions (van der Waals repulsion) between substituents within a molecule or between reacting molecules
Me C R O R H R OOH R H O R O H Br

General Reaction Types Radical Reactions (~10%):

Nu:

SN2

Me Nu C R R

Br:

A + B A(:) + B(+)
Lewis Acid

A A

B B

Polar Reactions (~90%):

major

Lewis Base
minor

FMO concepts extend the donor-acceptor paradigm to non-obvious families of reactions Consider stabilization energy (E) when bringing atoms A & B together:
Q: Charge density : Dielectric constant R: distance of A to B c: coefficient of MO m of species A, or MO n of species B : Overlap Integral E: Energy of MO

Nondirectional Electronic Effects (Inductive Effects):

Me R C R Br

SN1

+
R R C Me

+ Br:

rate decreases as R becomes more electronegative

E =

QAQB R Coulomb Term

2 mn

(cmAcnB)2 (Em - En)

Orbital Term

Fleming, page 27

D. A. Evans, F. Michael The H2 Molecule (again!!)

The H2 Molecular Orbitals

Chem 531

Linear Combination of Atomic Orbitals (LCAO): Orbital Coefficients Each MO is constructed by taking a linear combination of the individual atomic orbitals (AO): Bonding MO Antibonding MO = C11 + C22 =C*11 C*22

Let's combine two hydrogen atoms to form the hydrogen molecule. Mathematically, linear combinations of the 2 atomic 1s states create two new orbitals, one is bonding, and one antibonding:
Rule one: A linear combination of n atomic states will create n MOs. (antibonding) E
Energy

The coefficients, C1 and C2, represent the contribution of each AO. Rule Two: (C1)2 + (C2)2 = 1 The squares of the C-values are a measure of the electron population in neighborhood of atoms in question Rule Three: bonding(C1)2 + antibonding(C*1)2= 1 In LCAO method, both wave functions must each contribute one net orbital Consider the pi-bond of a C=O function: In the ground state pi-CO is polarized toward oxygen. Note (Rule 2) that the antibonding MO is polarized in the opposite direction.
C O

H 1

1s E

1s

H 2

(bonding)

Let's now add the two electrons to the new MO, one from each H atom:
(antibonding) E1
Energy

(antibonding)

H 1

1s E2

1s

H 2
Energy

(bonding)

Note that E1 is greater than E2. Why?

C O

(bonding)

D. A. Evans, F. Michael

Bonding Generalizations

Chem 531

Bond strengths (Bond dissociation energies) are composed of a covalent contribution ( Ecov) and an ionic contribution ( Eionic). Bond Energy (BDE) = Ecovalent + Eionic When one compares bond strengths between CC and CX, where X is some other element such as O, N, F, Si, or S, keep in mind that covalent and ionic contributions vary independently. Hence, the mapping of trends is not a trivial exercise.

Orbital orientation strongly affects the strength of the resulting bond.

For Bonds: A B Better than A B

For Bonds:

The following generalizations on covalent bonding are useful.

Overlap between orbitals of comparable energy is more effective than overlap between orbitals of differing energy. For example, consider elements in Group IV, Carbon and Silicon. We know that C-C bonds are considerably stronger by Ca. 20 kcal mol-1 than C-Si bonds.
C C C CC C

Better than

This is a simple notion with very important consequences. It surfaces in the delocalized bonding which occurs in the competing anti (favored) syn (disfavored) E2 elimination reactions. Review this situation. An anti orientation of filled and unfilled orbitals leads to better overlap. This is a corrollary to the preceding generalization. There are two common situations. Case-1: Anti Nonbonding electron pair & CX bond

better than

Si CSi

Si

X
Si-SP3 C-SP3 CC C-SP3 C-SP3 CSi

X A
lone pair HOMO

* CX LUMO

Better than

lone pair HOMO

X A C

* CX LUMO

H3CCH3 BDE = 88 kcal/mol Bond length = 1.534

H3CSiH3 BDE ~ 70 kcal/mol Bond length = 1.87

Case-2: Two anti sigma bonds

X C
CY HOMO

This trend is even more dramatic with pi-bonds: CC = 65 kcal/mol CSi = 36 kcal/mol SiSi = 23 kcal/mol Weak bonds will have corresponding low-lying antibonds.
Formation of a weak bond will lead to a corresponding low-lying antibonding orbital. Such structures are reactive as both nucleophiles & electrophiles A Y

Y
* CX LUMO

X C

Better than

CY HOMO

X C

* CX LUMO

D. A. Evans, F. Michael

Donor-Acceptor Properties of Bonding and Antibonding States

Chem 531

Donor Acceptor Properties of C-C & C-O Bonds Consider the energy level diagrams for both bonding & antibonding orbitals for C-C and C-O bonds.
* C-C * C-O

Hierarchy of Donor & Acceptor States Following trends are made on the basis of comparing the bonding and antibonding states for the molecule CH3-X where X = C, N, O, F, & H.
-bonding States: (CX)
CH3CH3 CH3H

C-sp

C-sp

3
CH3NH2

O-sp3 decreasing -donor capacity C-C C-O

CH3OH CH3F

poorest donor

The greater electronegativity of oxygen lowers both the bonding & antibonding C-O states. Hence:
C-C is a better donor orbital than C-O C-O is a better acceptor orbital than C-C

-anti-bonding States: (CX)

CH3H CH3CH3 CH3NH2 CH3OH

Donor Acceptor Properties of Csp3-Csp3 & Csp3-Csp2 Bonds

* C-C * C-C

better acceptor

Increasing -acceptor capacity

CH3F

best acceptor

C-sp3

C-sp3 C-sp2 C-C

The following are trends for the energy levels of nonbonding states of several common molecules. Trend was established by photoelectron spectroscopy.
Nonbonding States

better donor

C-C

H3P:

The greater electronegativity of Csp2 lowers both the bonding & antibonding CC states. Hence: Csp3-Csp2 is a better acceptor orbital than Csp3-Csp3 Csp3-Csp3 is a better donor orbital than Csp3-Csp2

H2S:

H3N: H2O: HCl:

poorest donor

decreasing donor capacity

D. A. Evans, F. Michael

Hybridization vs Electronegativity

Chem 531

Electrons in 2s states "see" a greater effective nuclear charge than electrons in 2p states.

This correctly implies that the stability of nonbonding electron pairs is directly proportional to the % of s-character in the doubly occupied orbital
Least stable Most stable

This becomes apparent when the radial probability functions for s and p-states are examined: The radial probability functions for the hydrogen atom s & p states are shown below.

Csp3

Csp2

Csp

The above trend indicates that the greater the % of s-character at a given atom, the greater the electronegativity of that atom.
100 % 100 %

Radial Probabilit y

Radial Probabilit y

1s Orbital

There is a linear relationship between %s character & Pauling electronegativity

2s Orbital

2s Orbital 2p Orbital

There is a direct relationship between %s character & hydrocarbon acidity

3s Orbital

3p Orbital

Electrons in s-states "see" a higher nuclear charge. This is even more obvious in an electron density map (see http://www.shef.ac.uk/chemistry/orbitron/). The s-orbitals have maximal electron density at the nucleus, and the p-orbitals have none.

D. A. Evans, F. Michael

Hyperconjugation: Carbocation Stabilization

Chem 531

The interaction of a vicinal bonding orbital with a p-orbital is referred to as hyperconjugation. This is a traditional vehicle for using valence bond to denote charge delocalization.
R H H C

Physical Evidence for Hyperconjugation

Bonds participating in the hyperconjugative interaction, e.g. CR, will be lengthened while the C(+)C bond will be shortened. First X-ray Structure of an Aliphatic Carbocation The Adamantane Reference (MM2) 1.431 1.608
Me Me Me Me Me H

+ +
C

R H H H H

+
C C H H

The graphic illustrates the fact that the C-R bonding electrons can "delocalize" to stabilize the electron deficient carbocationic center. Note that the general rules of drawing resonance structures still hold: the positions of all atoms must not be changed. Stereoelectronic Requirement for Hyperconjugation: coplanar orientation between interacting orbitals

[F5SbFSbF5]

100.6

+
C

110

1.528 1.530
Me

T. Laube, Angew. Chem. Int. Ed. 1986, 25, 349

The Molecular Orbital Description

CR CR

More substituted carbocations have more adjacent C-R bonds to act as donors to the empty p orbital Hence, more substituted carbocations are more stable.

+
C

H H

+
C

H H H

+ +
C

H H H H H C

+ +
C

H H H H H C

+ +
C

H CH3 H H H C

+ +
C

CH3 CH3

CR

CR
H H

+
C

bonding interaction
H H

Me least stable

1o

2o

3o most stable

Take a linear combination of CR and Csp2 p-orbital: The new occupied bonding orbital is lower in energy. When you stabilize the electrons in a system you stabilize the system itself.

D. A. Evans, F. Michael

"Negative" Hyperconjugation/Anomeric Effect

Syn Orientation
R H X H H H C X R: H H C X+ H H antibonding CR R: C H X H H C X+ R H H C antibonding CR R C X

Chem 531

Delocalization of nonbonding electron pairs into vicinal antibonding orbitals is also possible R H H C X H H H H R C

filled hybrid orbital

This delocalization is referred to as "negative" hyperconjugation

Anti Orientation
R H

Since nonbonding electrons prefer hybrid orbitals rather than p orbitals, this orbital can adopt either a syn or anti relationship to the vicinal CR bond.

filled X hybrid orbital

The Molecular Orbital Description

CR Overlap between two orbitals is better in the anti orientation as stated in "Bonding Generalizations" handout.

Nonbonding e pair

The Expected Structural Perturbations

Change in Structure
Shorter CX bond Longer CR bond

Spectroscopic Probe
X-ray crystallography X-ray crystallography Infrared Spectroscopy Infrared Spectroscopy NMR Spectroscopy NMR Spectroscopy

CR

As the antibonding CR orbital decreases in energy, the magnitude of this interaction will increase

Stronger CX bond Weaker CR bond Greater e-density at R Less e-density at X

D. A. Evans, F. Michael

The Anomeric Effect and Related Issues

The Anomeric Effect

Chem 531

Infrared evidence for lone pair delocalization into vicinal antibonding orbitals.
The NH stretching frequency of cis-methyl diazene is 200 cm-1 lower than the trans isomer. Me H H Me N N NH = 2188 cm Me N N H NH = 2317 cm -1
filled N-sp2
-1

It is not unexpected that the methoxyl substituent on a cyclohexane ring prefers to adopt the equatorial conformation. H OMe H

filled N-sp2

antibonding NH

Me N

antibonding N NH H

OMe G = +0.8 kcal/mol What is unexpected is that the closely related 2-methoxytetrahydropyran prefers the axial conformation: H O OMe G = 0.6 kcal/mol O H OMe

..

The low-frequency shift of the cis isomer is a result of NH bond weakening due to the anti lone pair on the adjacent (vicinal) nitrogen which is interacting with the NH antibonding orbital. Note that the orbital overlap is not nearly as good from the trans isomer.
N. C. Craig & co-workers JACS 1979, 101, 2480.

That effect which provides the stabilization of the axial OR conformer which overrides the inherent steric bias of the substituent is referred to as the anomeric effect. Principal HOMO-LUMO interaction from each conformation is illustrated below: H O OMe O H

Aldehyde CH Infrared Stretching Frequencies The IR CH stretching frequency for aldehydes is lower than the closely related olefin CH stretching frequency. For years this observation has gone unexplained.

OMe axial O lone pair CO preferred Since the antibonding CO orbital is a better acceptor orbital than the antibonding CH bond, the axial OMe conformer is better stabilized by R R this interaction which is worth ca 1.2 kcal/mol. R O Other electronegative substituents such as Cl, SR etc. also participate in C C C anomeric stabilization. H H R H 1.781 H CH = 2730 cm -1 CH = 3050 cm -1 O Cl H O O Cl We now conclude that this is another example of negative hyperconjugation. This conformer 1.819 Cl axial O lone pair CH
preferred by 1.8 kcal/mol Why is axial CCl bond longer ?